Edward M Schaeffer

Johns Hopkins Medicine, Baltimore, Maryland, United States

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Publications (115)473.67 Total impact

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    ABSTRACT: Current guidelines suggest adjuvant radiation therapy for men with adverse pathologic features (APFs) at radical prostatectomy (RP). We examine at-risk men treated only with RP until the time of metastasis. To evaluate whether clinicopathologic risk models can help guide postoperative therapeutic decision making. Men with National Comprehensive Cancer Network intermediate- or high-risk localized prostate cancer undergoing RP in the prostate-specific antigen (PSA) era were identified (n=3089). Only men with initial undetectable PSA after surgery and who received no therapy prior to metastasis were included. APFs were defined as pT3 disease or positive surgical margins. Area under the receiver operating characteristic curve (AUC) for time to event data was used to measure the discrimination performance of the risk factors. Cumulative incidence curves were constructed using Fine and Gray competing risks analysis to estimate the risk of biochemical recurrence (BCR) or metastasis, taking censoring and death due to other causes into consideration. Overall, 43% of the cohort (n=1327) had APFs at RP. Median follow-up for censored patients was 5 yr. Cumulative incidence of metastasis was 6% at 10 yr after RP for all patients. Cumulative incidence of metastasis among men with APFs was 7.5% at 10 yr after RP. Among men with BCR, the incidence of metastasis was 38% 5 yr after BCR. At 10 yr after RP, time-dependent AUC for predicting metastasis by Cancer of the Prostate Risk Assessment Postsurgical or Eggener risk models was 0.81 (95% confidence interval [CI], 0.72-0.97) and 0.78 (95% CI, 0.67-0.97) in the APF population, respectively. At 5 yr after BCR, these values were lower (0.58 [95% CI, 0.50-0.66] and 0.70 [95% CI, 0.63-0.76]) among those who developed BCR. Use of risk model cut points could substantially reduce overtreatment while minimally increasing undertreatment (ie, use of an Eggener cut point of 2.5% for treatment of men with APFs would spare 46% from treatment while only allowing for metastatic events in 1% at 10 yr after RP). Use of risk models reduces overtreatment and should be a routine part of patient counseling when considering adjuvant therapy. Risk model performance is significantly reduced among men with BCR. Use of current risk models can help guide decision making regarding therapy after surgery and reduce overtreatment. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    European Urology 04/2015; DOI:10.1016/j.eururo.2015.04.016 · 12.48 Impact Factor
  • Debasish Sundi, Edward M. Schaeffer, Ashley E. Ross
    European Urology 04/2015; DOI:10.1016/j.eururo.2015.03.038 · 12.48 Impact Factor
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    ABSTRACT: BACKGROUND The use of multidisciplinary clinics (MDCs) for outpatient cancer evaluation is increasing. MDCs may vary in format, and data on whether MDCs change prostate cancer (PCa) care are limited. Here we report on the setup and design of a relatively new PCa MDC clinic. Because MDC evaluation was associated with a comprehensive re-evaluation of all patients' staging and risk stratification data, we studied the frequency of changes in PCa grade and stage upon MDC evaluation, which provides a unique estimate of the magnitude of pathology, radiology, and exam-based risk stratification in a modern tertiary setting.METHODS In 2008–2012, 887 patients underwent consultation for newly diagnosed PCa at the Johns Hopkins Hospital (JHH) weekly MDC. In a same-day process, patients are interviewed and examined in a morning clinic. Examination findings, radiology studies, and biopsy slides are then reviewed during a noon conference that involves real-time collaboration among JHH attending specialty physicians: urologists, radiation oncologists, medical oncologists, pathologists, and radiologists. During afternoon consultations, attending physicians appropriate to each patient's eligible treatment options individually meet with patients to discuss management strategies and/or clinical trials. Retrospective chart review identified presenting tumor characteristics based on outside assessment, which was compared with stage and grade as determined at MDC evaluation.RESULTSOverall, 186/647 (28.7%) had a change in their risk category or stage. For example, 2.9% of men were down-classified as very-low-risk, rendering them eligible for active surveillance. 5.7% of men thought to have localized cancer were up-classified as metastatic, thus prompting systemic management approaches. Using NCCN guidelines as a benchmark, many men were found to have undergone non-indicated imaging (bone scan 23.9%, CT/MRI 47.4%). The three most chosen treatments after MDC evaluation were external beam radiotherapy ± androgen deprivation (39.3%), radical prostatectomy (32.0%), and active surveillance/expectant management (12.9%).CONCLUSIONSA once-weekly same-day evaluation that involves simultaneous data evaluation, management discussion, and patient consultations from a multidisciplinary team of PCa specialists is feasible. Comprehensive evaluation at a tertiary referral center, as demonstrated in a modern MDC setting, is associated with critical changes in presenting disease classification in over one in four men. Prostate © 2014 Wiley Periodicals, Inc.
    The Prostate 02/2015; 75(2). DOI:10.1002/pros.22904 · 3.57 Impact Factor
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    ABSTRACT: To report race-based outcomes after radical prostatectomy (RP) in a cohort stratified by National Comprehensive Cancer Network (NCCN) risk category with updated follow-up. Studies describing racial disparities in outcomes after RP are conflicting. We studied 15,993 white and 1634 African American (AA) pretreatment-naïve men who underwent RP at our institution (1992-2013) with complete preoperative and pathologic data. Pathologic outcomes were compared between races using appropriate statistical tests; biochemical recurrence (BCR) for men with complete follow-up was compared using multivariate models that controlled separately for preoperative and postoperative covariates. Very low- and low-risk AA men were more likely to have positive surgical margins (P <.01), adverse pathologic features (P <.01), and be upgraded at RP (P <.01). With a median follow-up of 4.0 years after RP, AA race was an independent predictor of BCR among NCCN low-risk (HR, 2.16; P <.001) and intermediate-risk (hazard ratio [HR], 1.34; P = .024) classes and pathologic Gleason score ≤6 (HR, 2.42; P <.001) and Gleason score 7 (HR, 1.71; P <.001). BCR-free survival for very low-risk AA men was similar to low-risk white men (P = .890); BCR-free survival for low-risk AA men was similar to intermediate-risk white men (P = .060). When stratified by NCCN risk, AA men with very low-, low-, or intermediate-risk prostate cancer who undergo RP are more likely to have adverse pathologic findings and BCR compared with white men. AA men with "low risk" prostate cancer, especially those considering active surveillance, should be counseled that their recurrence risks can resemble those of whites in higher risk categories. Copyright © 2014 Elsevier Inc. All rights reserved.
    Urology 12/2014; 84(6):1434-41. DOI:10.1016/j.urology.2014.08.039 · 2.13 Impact Factor
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    Nilay M. Gandhi, Joseph Lin, Edward Schaeffer
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    ABSTRACT: Prostate postbiopsy infectious complications typically present in the form of prostatitis and uncommonly urosepsis. Prostatic abscesses are generally found after multiple bouts of prostatitis and are associated with a clinically septic picture requiring intensive care unit admission and resuscitation. We report the case of a 65-year-old man who presented with prostatic abscess in the setting of nonspecific urinary symptoms after transrectal ultrasonography–guided prostate biopsy. At 4-month follow-up, he is currently free of disease with undetectable prostate-specific antigen level and negative imaging.
    11/2014; DOI:10.1016/j.eucr.2014.08.005
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    ABSTRACT: Objective To assess the association between magnetic resonance (MR) appearance of prostate cancer on a baseline multiparametric prostate (MP) MR imaging (MRI) and biopsy outcome in men with favorable-risk prostate cancer managed with active surveillance (AS). Materials and Methods Ninety-six consecutive men (mean age, 67.8 years) who had a baseline MP MRI within 1 year of AS enrollment were included in the study. MP MRI results were analyzed to identify men with MR-invisible tumor defined as no signal abnormality on T2-weighted images, no focal restricted diffusion, and no perfusion abnormality on dynamic contrast-enhanced images. Patients with (n = 84) or without (n = 12) MR-visible tumor were compared and the impact of MR-invisibility of tumor on the risk of adverse biopsy pathology based on the Epstein criteria was investigated with a median follow-up of 23 months. Results Adverse biopsy pathology occurred in 36.5% (35 of 96) of patients. There was no significant difference in the fulfillment of AS criteria at enrollment, prostate-specific antigen level or density, prostate volume, and number of biopsies (total or after MRI) between the 2 groups of patients. A total of 8.3% (1 of 12) of men with MR-invisible tumor had adverse biopsy pathology as compared with 40.5% (34 of 84) of men with MR-visible tumors. The MR-invisibility of tumor was associated with a lower risk of adverse biopsy pathology (crude relative risk = 0.35; 95% confidence interval, 0.10-1.25; prostate-specific antigen density–adjusted relative risk = 0.21; 95% confidence interval, 0.03-1.32). Conclusion The MR-invisibility of tumor on MP MRI could be of prognostic significance in monitoring men in AS with potential benefit of tailoring the frequency of surveillance biopsies and reducing the number of unnecessary biopsies.
    Urology 10/2014; DOI:10.1016/j.urology.2014.06.085 · 2.13 Impact Factor
  • Debasish Sundi, Edward M Schaeffer
    Urology 10/2014; DOI:10.1016/j.urology.2014.06.065 · 2.13 Impact Factor
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    ABSTRACT: Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of CP1, a human prostatic isolate of Escherichia coli. CP1 bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles with chronic inflammation lasting at least one year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist despite decreased expression of androgen receptor (AR). Inflammatory cells in the prostates of CP1 infected mice were characterized at 8 weeks post-infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, CP1 infection in the Hi-Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma with 70% more mice developing cancer by 4.5 months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression, and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression.
    The Journal of Pathology 10/2014; 235(3). DOI:10.1002/path.4472 · 7.33 Impact Factor
  • Edward M. Schaeffer
    The Journal of Urology 09/2014; 192(3). DOI:10.1016/j.juro.2014.05.098 · 3.75 Impact Factor
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    ABSTRACT: Rectal swabs can identify men with fluoroquinolone (FQ)-resistant bacteria and reduce rates of infection after transrectal ultrasound guided prostate biopsy (TRUSB) by targeted antimicrobial prophylaxis. We evaluated the rate of FQ resistance in an active surveillance cohort with attention to factors associated with resistance and changes in resistance over time.
    The Journal of urology 08/2014; DOI:10.1016/j.juro.2014.08.008 · 3.75 Impact Factor
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    ABSTRACT: Objective To investigate the post-prostatectomy and long-term outcomes of men presenting with an elevated pretreatment prostate-specific antigen (PSA) level (>10ng/mL), but otherwise low-risk features (biopsy Gleason score 6 and clinical stage T2a). Patients and MethodsPSA-incongruent intermediate-risk (PII) cases were defined as those patients with preoperative PSA >10 and 20ng/mL but otherwise low-risk features, and PSA-incongruent high-risk (PIH) cases were defined as men with PSA >20ng/mL but otherwise low-risk features. Our institutional radical prostatectomy database (1992-2012) was queried and the results were stratified into D'Amico low-, intermediate- and high risk, PSA-incongruent intermediate-risk and PSA-incongruent high-risk cases. Prostate cancer (PCa) features and outcomes were evaluated using appropriate comparative tests. Multivariable analyses were adjusted for age, race and year of surgery. ResultsOf the total cohort of 17 608 men, 1132 (6.4%) had PII-risk disease and 183 (1.0%) had PIH-risk disease. Compared with the low-risk group, the odds of upgrading at radical prostatectomy (RP) were 2.20 (95% CI 1.93-2.52; P < 0.001) for the PII group and 3.58 (95% CI 2.64-4.85; P < 0.001) for the PIH group, the odds of extraprostatic disease at RP were 2.35 (95% CI 2.05-2.68; P < 0.001) for the PII group and 6.68 (95% CI 4.89-9.15; P < 0.001) for the PIH group, and the odds of positive surgical margins were 1.97 (95% CI 1.67-2.33; P < 0.001) for the PII group and 3.54 (95% CI 2.50-4.95, P < 0.001) for the PIH group. Compared with low-risk disease, PII-risk disease was associated with a 2.85-, 2.99- and 3.32-fold greater risk of biochemical recurrence (BCR), metastasis and PCa-specific mortality, respectively, and PIH-risk disease was associated with a 5.32-, 6.14- and 7.07-fold greater risk of BCR, metastasis and PCa-specific mortality, respectively (P 0.001 for all comparisons). For the PII group, the higher risks of positive surgical margins, upgrading, upstaging and BCR were dependent on PSA density (PSAD): men in the PII group who had a PSAD <0.15ng/mL/g were not at higher risk compared with those in the low-risk group. Men in the PII group with a PSAD 0.15ng/mL/g and men in the PIH group were more likely to have an anterior component of the dominant tumour (59 and 64%, respectively) compared with those in the low- (35%) and intermediate-risk group (39%) and those in the PII-risk group with PSAD <0.15ng/mL/g (29%). Conclusions Men with PSA >20ng/mL or men with PSA >10 and 20ng/mL with a PSAD 0.15ng/mL/g, but otherwise low-risk PCa, are at greater risk of adverse pathological and oncological outcomes and may be inappropriate candidates for active surveillance. These men are at greater risk of having anterior tumours that are undersampled at biopsy, so if treatment is deferred, ancillary testing such as anterior zone sampling or magnetic resonance imaging should be strongly encouraged. Men with elevated PSA levels >10 and 20ng/mL but low PSAD have outcomes similar to those in the low-risk group, and consideration of surveillance is appropriate in these cases.
    BJU International 04/2014; 114(6B). DOI:10.1111/bju.12771 · 3.13 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e457. DOI:10.1016/j.juro.2014.02.1234 · 3.75 Impact Factor
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    ABSTRACT: Objective To evaluate the risk of reclassification on serial biopsy for Caucasian and African American (AA) men with very low-risk (VLR) prostate cancer enrolled in a large prospective active surveillance (AS) registry. Methods The Johns Hopkins AS registry is a prospective observational study that has enrolled 982 men since 1994. Including only men who met all National Comprehensive Cancer Network VLR criteria (clinical stage ≤T1, Gleason score ≤6, prostate-specific antigen [PSA] level <10 ng/mL, PSA density <0.15 ng/mL/cm3, positive cores <3, percent cancer per core ≤50), we analyzed a cohort of 654 men (615 Caucasians and 39 AAs). The association of race with reclassification on serial biopsy was assessed with competing-risks regressions. Results AA men on AS were more likely than Caucasians to experience upgrading on serial biopsy (36% vs 16%; adjusted P <.001). Adjusting for PSA level, prostate size, volume of cancer on biopsy, treatment year, and body mass index, AA race was an independent predictor of biopsy reclassification (subdistribution hazard ratio, 1.8; P = .003). Examining specific modes of reclassification, AA race was independently associated with reclassification by grade (subdistribution hazard ratio, 3.0; P = .002) but not by volume. Conclusion AA men with VLR prostate cancer followed on AS are at significantly higher risk of grade reclassification compared with Caucasians. Therefore, if the goal of AS is to selectively monitor men with low-grade disease, AA men may require alternate selection criteria.
    Urology 04/2014; DOI:10.1016/j.juro.2014.02.1661 · 2.13 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e593. DOI:10.1016/j.juro.2014.02.1643 · 3.75 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e898-e899. DOI:10.1016/j.juro.2014.02.2432 · 3.75 Impact Factor
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    ABSTRACT: Notch signalling is implicated in the pathogenesis of a variety of cancers, but its role in prostate cancer is poorly understood. However, selected Notch pathway members are overrepresented in high-grade prostate cancers. We comprehensively profiled Notch pathway components in prostate cells and found prostate cancer-specific up-regulation of NOTCH3 and HES6. Their expression was particularly high in androgen responsive lines. Up- and down-regulating Notch in these cells modulated expression of canonical Notch targets, HES1 and HEY1, which could also be induced by androgen. Surprisingly, androgen treatment also suppressed Notch receptor expression, suggesting that androgens can activate Notch target genes in a receptor-independent manner. Using a Notch-sensitive Recombination signal binding protein for immunoglobulin kappa J region (RBPJ) reporter assay, we found that basal levels of Notch signalling were significantly lower in prostate cancer cells compared to benign cells. Accordingly pharmacological Notch pathway blockade did not inhibit cancer cell growth or viability. In contrast to canonical Notch targets, HES6, a HES family member known to antagonize Notch signalling, was not regulated by Notch signalling, but relied instead on androgen levels, both in cultured cells and in human cancer tissues. When engineered into prostate cancer cells, reduced levels of HES6 resulted in reduced cancer cell invasion and clonogenic growth. By molecular profiling, we identified potential roles for HES6 in regulating hedgehog signalling, apoptosis and cell migration. Our results did not reveal any cell-autonomous roles for canonical Notch signalling in prostate cancer. However, the results do implicate HES6 as a promoter of prostate cancer progression. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
    European Urology Supplements 04/2014; 13(1):e847. DOI:10.1016/S1569-9056(14)60834-4 · 3.37 Impact Factor
  • Edward M Schaeffer
    The Journal of urology 02/2014; 191(2):361-2. DOI:10.1016/j.juro.2013.10.123 · 3.75 Impact Factor
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    ABSTRACT: Purpose Of men with very low risk prostate cancer at biopsy recent evidence shows that black American men are at greater risk for adverse oncologic outcomes after radical prostatectomy. We studied radical prostatectomy specimens from black and white men at very low risk to determine whether there are systematic pathological differences. Materials and Methods Radical prostatectomy specimens were evaluated in men with National Comprehensive Cancer Network® (NCCN) very low risk prostate cancer. At diagnosis all men underwent extended biopsy sampling (10 or more cores) and were treated in the modern Gleason grade era. We analyzed tumor volume, grade and location in 87 black and 89 white men. For each specimen the dominant nodule was defined as the largest tumor with the highest grade. Results Compared to white men, black men were more likely to have significant prostate cancer (61% vs 29%), Gleason 7 or greater (37% vs 11%, each p <0.001) and a volume of greater than 0.5 cm3 (45% vs 21%, p = 0.001). Dominant nodules in black men were larger (median 0.28 vs 0.13 cm3, p = 0.002) and more often anterior (51% vs 29%, p = 0.003). In men who underwent pathological upgrading the dominant nodule was also more frequently anterior in black than in white men (59% vs 0%, p = 0.001). Conclusions Black men with very low risk prostate cancer at diagnosis have a significantly higher prevalence of anterior cancer foci that are of higher grade and larger volume. Enhanced imaging or anterior zone sampling may detect these significant anterior tumors, improving the outcome in black men considering active surveillance.
    The Journal of Urology 01/2014; 191(1):60–67. DOI:10.1016/j.juro.2013.06.021 · 3.75 Impact Factor
  • Debasish Sundi, Edward M Schaeffer
    Oncology (Williston Park, N.Y.) 01/2014; 28(1):83, 85. · 2.98 Impact Factor

Publication Stats

1k Citations
473.67 Total Impact Points

Institutions

  • 2003–2015
    • Johns Hopkins Medicine
      • Department of Urology
      Baltimore, Maryland, United States
  • 2014
    • Detroit Medical Center
      Detroit, Michigan, United States
  • 2008–2014
    • Johns Hopkins University
      • • Department of Pathology
      • • Department of Medicine
      Baltimore, Maryland, United States
    • North Shore-Long Island Jewish Health System
      New York, New York, United States
  • 2013
    • Memorial Sloan-Kettering Cancer Center
      New York, New York, United States
  • 2007
    • George Washington University
      Washington, Washington, D.C., United States